Kinase requirements in human cells: I. Comparing kinase requirements across various cell types.
shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: (i) in repeat experiments using the same cells, (ii) with multiple populations of freshly prepared primary epithelial cells isolated from the same tissue source, and (iii) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this study suggest that the control of proliferation and survival may be significantly different between cell lines and that simple comparisons from any one cell to another may be misleading. Although the regulation of cell proliferation and survival are heavily studied areas, we did not see a bias in these screens toward the identification of previously known and well studied kinases, suggesting that our knowledge of molecular events in these areas is still meager.
Grueneberg
Dorre A
DA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Degot
Sebastien
S
Pearlberg
Joseph
J
Li
Wenliang
W
Davies
Joan E
JE
Baldwin
Amy
A
Endege
Wilson
W
Doench
John
J
Sawyer
Jacqueline
J
Hu
Yanhui
Y
Boyce
Frederick
F
Xian
Jun
J
Munger
Karl
K
Harlow
Ed
E
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002477:Cells / Q000166:cytology / Q000201:enzymology*; D002478:Cells, Cultured; D020868:Gene Silencing; D006801:Humans; D010770:Phosphotransferases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering
D034741:RNA, Small Interfering; D010770:Phosphotransferases